The polyethylene glycol is an extremely versatile polyether high molecular weight compounds, it can be used in many fields such as medicine, health, food, chemical, etc. Polyethylene glycol can be dissolved in water and many solvents and the polymer has excellent biocompatibility, can be dissolved in tissue fluid in vivo, can be rapidly excreted from the body without any toxic side effects.
In application of polyethylene glycol, end group plays a decisive role, different end groups of the polyethylene glycol has a different use. The polyethylene glycol polymeric chain segment is not limited to the terminal hydroxyl group, polyethylene glycol active derivative obtained through the introduction of other functionalized end groups such as amino, carboxyl, aldehyde group and the like, can greatly broaden the range of applications of polyethylene glycol, making it has a broad application prospect in organic synthesis, peptide synthesis, polymer synthesis and sustained release or controlled release of drugs, targeting administration, etc.
Polyethylene glycol active derivative has been reported in many document.
Patent document U.S. Pat. No. 5,672,662 describes the preparation of linear polyethylene glycols having an end group of propionic acid and butyric acid, and the n-hydroxy succinimide ester thereof.
Patent document U.S. Pat. No. 5,643,575 describes a u-shaped structure polyethylene glycol derivative.
Non-patent document “synthesis and curing of terminal alkyne groups polyethylene glycol” (Chinese Journal of Explosives & Propellants, December 2010, vol 33, no. 6) describes a synthesis method of alkynyl-terminated polyethylene glycol, including polyethylene glycol 400 and propyne bromine as raw materials, tetrahydrofuran as solvent, reaction in the presence of catalyst potassium tert-butoxide to obtain the product, however, the prepared polymer is a linear polyethylene glycol, it can be introduced two terminal alkyne groups at most, and can not be introduced into the other active groups.
Patent document WO 2011075953 A1 describes a novel multi-arm polyethylene glycol having different type of active groups, which formed by the polymerization of ethylene oxide, and an oligomeric pentaerythritol as the initiator. The active end group is selected from the group consisting of hydroxyl, amino, sulfhydryl, carboxyl, ester group, aldehyde group, acrylic and maleic imide group, it does not disclose active end group may be alkynyl.
To overcome the deficiencies of the prior art, the present invention provides an alkynyl multi-arm polyethylene glycol active derivative and a preparation method thereof.